Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus

Erythropoietin (Epo) produced by the kidney regulates erythropoiesis. Recen t evidence suggests that Epo in the cerebrum prevents neuron death and Epo in the uterus induces estrogen (E-2)-dependent uterine angiogenesis. To elu cidate how Epo expression is regulated in these tissues, ovariectomized mic e were given E-2 and/or exposed to hypoxia, and the temporal patterns of Ep o mRNA levels were examined. Epo mRNA levels in the kidney and cerebrum wer e elevated markedly within 4 h after exposure to hypoxia. Although the elev ated level of Epo mRNA in the kidney decreased markedly within 8 h despite continuous hypoxia, the high level in the cerebrum was sustained for greate r than or equal to 24 h, indicating that downregulation operates in the kid ney but not in the brain. E-2 transiently induced Epo mRNA in the uterus bu t not in the kidney and cerebrum. Interestingly, the uterine Epo mRNA was h ypoxia inducible only in the presence of E-2. Thus Epo expression appears t o be regulated in a tissue-specific manner, endorsing the tissue-specific f unctions of Epo.